It has been previously reported that prior nasal administration of the highly attenuated strain of Bordetella pertussis, BPZE1, provides effective and sustained protection against lethal challenge with influenza A viruses at least by suppressing the production of major pro-inflammatory mediators [1 and PCT/US2009/047399].
Asthma is a chronic inflammatory lung disease characterized by intermittent airflow obstruction, airway hyperreactivity (AHR), mucus hypersecretion, enhanced IgE responses and infiltration of inflammatory cells—mainly eosinophils into the airways (2). In recent years, the incidence of asthma has increased dramatically, with the greatest prevalence observed in developed countries (3). Although altered Th2/Th1 balance with a Th2-dominant immune response has been shown to be important in the development of asthma, the mechanism underlying the pathogenesis of asthma remains to be fully deciphered (4).
Allergic contact dermatitis (ACD) caused by reactive haptens and metal ions is a form of delayed type hypersensitivity, and is one of the most common skin diseases worldwide (5). Contact hypersensitivity (CHS) is a recognized mouse model for studying human ACD and is an epidermal T cell-mediated inflammatory response to low molecular weight haptens (6,7).
According to the hygiene hypothesis, frequent exposure to pathogens triggers a certain degree of protective immunity against atopic diseases (8). However, conflicting observations have been reported regarding the protective versus detrimental role of the pre-exposure to viral or bacterial microorganisms against allergic diseases (9-13), underscoring that the effect of encounter with pathogenic and nonpathogenic bacteria on shaping the host immune response is complex and remains poorly understood. Furthermore, despite intensive studies on the mechanisms and optimal medical management, current therapeutic approaches that tackle these inflammatory disorders are largely ameliorative rather than curative and can cause unexpected side effects (14). In addition many asthmatic patients develop resistance to treatment and/or progressive pulmonary dysfunction (14). Thus there remains an ongoing need for better therapies to treat allergic diseases, such as those described herein.